BMC Neurology BioMed Central Study protocol

Background Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function. Method/Design Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls. Discussion By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia. Trial Registration The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov


Discussion:
This study aims to establish and evaluate community-based sustainable exercise programs for stroke survivors. We will determine the effects of the exercise programs in preventing falls and enhancing mobility among people following stroke. This program, if found to be effective, has the potential to be implemented within existing community services.
Trial registration: The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000479505).

Background
Stroke is a leading cause of death and disability. The annual estimated direct and indirect costs of stroke in the US in 2009 is $68.9 billion [1]. The major burden of stroke is chronic disability rather than death [2]. It is projected that stroke-related disability will increase dramatically over the next two decades as the population ages [3]. Development and implementation of effective strategies to minimise stroke-related disability is essential to minimise future health costs.
On completion of rehabilitation most stroke survivors can walk independently, however 90% of these people are unable to walk with sufficient speed or endurance to function effectively in the community [4] and 70% of stroke survivors will fall within six months of discharge from hospital [5]. Gait and balance problems have been found to be important risk factors for falls in stroke survivors [6,7]. Walking speed and walking capacity among community dwelling stroke survivors is markedly lower than age-matched controls [8,9], which results in major limitations of community participation.
Stroke typically affects older persons. The development of effective strategies to minimise disability and falls among older people is an urgent public health challenge due to the increase of older people in the global population. Around 500 million people worldwide are aged 65 and older and this number is predicted to increase to 1 billion by 2020 [10]. Falls adversely affect the quality of life of older people and can have serious consequences including fractures. Stroke survivors are four times more likely to suffer a hip fracture than other community-dwellers [11]. Systematic reviews in the general older population have found that exercise programs which specifically target balance and lower limb muscle strength are effective in preventing falls [12,13]. It is less clear whether exercise can prevent falls among people following stroke. There is also good evidence that well-designed exercise programs can enhance functional abilities after stroke [14]. Previous work has shown the effectiveness of small-group "circuitstyle" exercise programs among people following stroke [15] or other disabling conditions [16] for improving mobility. Previously it was thought that recovery follow-ing stroke occurs within the first three months and is complete by 12 months [17]. However there is growing evidence that functional abilities can improve with exercise many years after stroke [9,18,19] The Weight-bearing Exercise for Better Balance (WEBB) exercise program has been developed by two of the authors (CS and CMD) and colleagues to specifically target poor balance and lower limb muscles weakness for people at risk of falls. The main aim of this randomised controlled trial is to determine the effectiveness of the WEBB exercise program on reducing falls and enhancing mobility among community dwelling stroke survivors. In addition we will measure the effects of the program on risk of falling, physical activity levels, community participation, quality of life and health service utilisation. The WEBB program is available on request from the first author. A secondary aim of the trial is to evaluate the effect of the upper limb/cognitive intervention program, on upper limb function and cognition.

Methods/design
Design A randomised controlled trial will be conducted with three hundred and fifty community-dwelling stroke survivors ( Figure 1).

Participant selection
Participants will be randomly assigned to one of two intervention groups and will be primarily recruited through the Stroke Recovery Association of New South Wales (NSW), Australia support group (Stroke Club) network. This Association holds regular Stroke Club meetings throughout NSW. The exercise classes will be conducted weekly in the venues used by the Stroke Club, prior to and after meeting times. It is anticipated that each Stroke Club will have participants randomised into both intervention groups and both types of classes will be offered at different times at the same venue. Additional participants will be recruited through advertisement and local physiotherapists and will attend the same exercise classes. To be eligible for the study, participants must be communitydwelling stroke survivors aged 40 years and above and be able to walk 10 m independently with or without a mobility aid.
Participants will be excluded if they have a Mini-Mental State Examination score [20] of < 20, have insufficient communication skills to participate in assessment and intervention, have a medical condition which precludes exercise (eg. unstable cardiovascular disease) or suffer from other uncontrolled chronic conditions that would interfere with the safety and conduct of the training and testing protocol.
All potential volunteers will be screened for eligibility by a physiotherapist. Medical clearance will be required from each participant's medical practitioner to certify him/her able to participate in moderate-intensity semi-supervised exercise before being accepted into the trial.
The study protocol has been approved by Sydney South West Area Health Service Ethics Committee (Clearance No: X06-0039) and The University of Sydney Human Research Ethics Committee (HREC Number 07/2006/ 9031), and written informed consent will be obtained from all participants.

Measurements and Procedures
All participants will undergo two measurements: one on entry to the study (pre-test) and one after the 12-month period (post-test) by a physiotherapist blinded to group allocation. All pre-test measures will be completed prior to randomisation.

Randomisation
After approval from the participant's usual General Practitioner and completion of the initial assessment, participants will be formally entered into the study and randomised to either the lower limb intervention or upper limb/cognition intervention group. Randomisation will be stratified by stroke club site using a computer generated random number schedule with variable block sizes 2-6. Generation of the randomisation sequence will be Trial design Pr e-test measur ement performed centrally by a researcher not involved in recruitment or assessment. Group allocation will be concealed using consecutively-numbered opaque envelopes.
The opaque envelope will be opened after completion of the assessment in the presence of the participant.

Intervention groups
Both intervention groups will receive weekly exercise classes and a home program for twelve months. The home programs will be reviewed monthly by a physiotherapist and modified if necessary.

Lower limb group
The lower limb intervention group will receive an exercise intervention designed to prevent falls, enhance mobility and increase physical activity. This will involve a weekly circuit-style group exercise class, a home exercise program and a walking program. Interventions will be tailored to an individual's functional ability and the nature and difficulty of exercises will be progressed regularly.
The lower limb group will undertake exercises from the WEBB program. Participants will participate in a weekly exercise classes conducted by a physiotherapist and will be asked to perform a home exercise program at least 3 times a week. The home program and exercise classes include a 45-60 min program of progressive balance, lower limb strengthening exercises and walking. The exercise classes and home program will include 5 minutes warm-up exercises. The lower limb extensor muscle groups, which act to prevent collapse of the lower limb (hip and knee extensors and ankle plantarflexors) will be targeted with exercises designed to enhance balance and muscle strength. The balance exercises include standing with a decreased base of support, forwards and sideways stepping/walking, and graded reaching activities in standing. Strengthening exercises will include sit-to-stand, forward or lateral step-ups onto a small block, semi squats and heel raises in standing. Resistance for strengthening exercises will be applied using weighted vests in a similar protocol to one which has been successfully used by people with multiple sclerosis in a home-based program [21]. Standard principles governing frequency, volume, duration, intensity and progression of exercise will be applied [22].

Upper limb/cognition group
The upper limb/cognition intervention group will receive a weekly exercise class aimed at management and improved function of the affected upper limb and cognition, carried out in the seated position. They will also be given a home exercise program. The upper limb component of the intervention was designed and developed by one of authors RB. We postulate that this intervention may lead to improvements in upper limb function and cognition but is unlikely to affect change in falls and mobility. This study design will, therefore, enable assessment of additional benefits of the lower limb intervention over and above likely benefits of social aspects of exercise classes.

Safety
Participants will be instructed how to perform exercises safely with a stable object (such as a table) located nearby for additional support if required. Participants will be provided with a booklet containing safety precautions, instructions and photographs of exercises for use in exercise sessions at home. In addition, they will be provided with a logbook for recording exercises completed, effects of exercise (e.g. muscle soreness). Where appropriate, family members and/or carers, will be encouraged to assist with supervision and performance of the exercise program.

Outcome measures
The primary outcome measures will be falls and mobility. Falls will be defined as "events that resulted in a person coming to rest unintentionally on the ground or other lower level, not as the result of a major intrinsic event or an overwhelming hazard" [23]. Falls will be assessed by comparing the number of falls in intervention and control groups. The proportion of fallers in each group will also be compared. Falls will be monitored for one year with monthly fall calendars. All participants will receive monthly calendars on entry to the study, with instructions to record the following events: number of falls, visits to or by nursing and allied health personnel, general practitioner or specialists appointments and hospitalisations. Participants will be asked to return the completed calendar monthly at their weekly exercise class. If calendars are not returned, further contact will be made by telephone. Details of any falls (including how and where the fall occurred, injuries suffered, medical intervention required and limitations to activity as a result of a fall) will be verified.
Two aspects of mobility, walking speed and capacity will be assessed. Walking speed will be measured using the 10 m walk test. Participants will be timed as they walk at their comfortable speed over the middle 10 m of a level 14 m walk track. Walking capacity will be measured by the distance covered in the 6 min walk test. The test will be conducted over a 25 -30 m level corridor and standardised instructions will be given to each participant prior to the test and standardised encouragement at each minute in accordance with the American Thoracic Society guidelines for the 6 min walk test [24]. For safety, while administering this test, the assessor will walk slightly behind, and not beside, the participant so as to avoid influencing the participant's self selected walking pace.
Secondary outcome measures listed below will be collected on entry and at the end of the 12-month study period. These outcome measures will be i) Falls risk assessed using the Physiological Profile Assessment [25] ii) Physical activity assessed via a 7-day pedometer count iii) Community participation using the Adelaide activity profile [26] iv) Quality of life and well-being using the SF 12™ Version 2 v) Health service utilisation using monthly calendars vi) Upper limb function using Items 6,7,8 of Motor Assessment Scale for Stroke [27] and the nine hole peg test [28] vii) Cognition using the Montreal Cognitive Assessment [29].

Statistical analysis
The number of falls per person-year will be analysed using negative binomial regression to estimate the difference in fall rates between the two groups, adjusted for previous multiple faller status [30]. The proportion of fallers between groups will be compared using the relative risk statistic. Between-group comparisons of final test performance for the continuously-scored outcome measures will be made using General Linear Models (ANCOVA) controlled for pre-test performance. Ordinally-scored data will be analysed for between group differences using the non-parametric Mann Whitney U statistic. An intentionto-treat approach will be used for all analyses.

Sample size
As fall rates will be compared between groups using incident rate ratios (IRR) from negative bionomial regression models [30] we conducted an analysis of statistical power using the nbpower command in the STATA software package. A total of 350 participants (175 per group) will be recruited. The study will have 80% power to detect as significant at the 5% level a 34% reduction in the rate of falling (i.e. an IRR of 0.66 using negative binomial regression analysis) in the 12 month follow-up period. This allows for a 15% loss to follow-up due to death or withdrawal from the study. Experience from our previous work indicates that, with this sample size, power will also be sufficient to detect meaningful between-group differences for all other outcome measures [9,15,16].

Discussion
It is widely accepted that in order to maintain health, physical activity is essential. Currently in the study area, routine provision of long term ongoing physical activity/ exercise programs for people living in the community after stroke is virtually non-existent. There are a range of community-based physical activity programs for healthy older people. However, the chronic disability often associated with stroke means that these programs are not usually accessible for this population.
There is an urgent need to identify cost-effective evidencebased interventions for reducing falls and related injuries in people who has had a stroke. The WEBB program has been designed for falls prevention and so includes high challenge, yet safe, progressive balance exercises targeting standing balance and walking as well as progressive moderate to high intensity leg strengthening exercises with resistance applied using weighted vests. The program is currently also being evaluated in older persons recently discharged from hospital [31] and people with Parkinson's disease [32].
This project aims to investigate the effects of the WEBB program in community dwelling stroke survivors using a randomised controlled trial incorporating the features known to reduce bias (i.e. concealed random allocation to groups, blinded outcome assessment and intention to treat analysis) and large enough to detect any effect of the intervention on fall rates. This project will determine the effectiveness of the exercise intervention in reducing falls and enhance physical activity. In addition, we will also provide new knowledge about the potential for collaborating with existing community support groups in the provision of physical activity programs. Due to the partnership with NSW Stroke Recovery Association and their extensive network of stroke clubs, there is good potential for the proposed program to be incorporated into usual Stroke Club activities at the completion of the study period, if it is found to be effective. If this community-based exercise intervention is effective, this approach of utilising support groups could also have wide applications for other chronic diseases which are worsened by inactivity.